Drugs that block
norepinephrine reuptake offer promise as
opioid potentiators, because
norepinephrine mediates
opioid analgesia but not side effects such as sedation or
nausea. In a two-by-two factorial design, we randomized 62 inpatients with
pain following major surgery to receive either
desipramine, 50 mg by mouth, or placebo at 6 a.m. on the first day after surgery. At their first request of
pain medication after 8 a.m., they were given intravenous
morphine, either 0.033 mg/kg or 0.10 mg/kg.
Pain relief and side effects were assessed for 4 hr; peak relief on the visual analog scale (VAS) was the primary outcome variable.
Pain relief, side effect scores, and time to remedication were significantly greater with the higher dose than with the lower dose of
morphine, verifying assay sensitivity, but
desipramine pretreatment did not significantly enhance
morphine analgesia. The mean increase in peak VAS relief score after
desipramine pretreatment, relative to placebo, was 6%; the 95% confidence interval for this estimate ranged from a 21% reduction to a 34% increase in
pain relief. These results differ from a previous report that 1 week of pretreatment with
desipramine, 75 mg per day, potentiated postoperative
morphine analgesia. We conclude that if
desipramine potentiation of
opioid analgesia occurs in humans, its demonstration may require higher doses or chronic treatment.